Objective To study the relationship between the single nucleotide polymorphisms (SNP)of X-ray repair cross-complementing group-3(XRCC3),human 8-hydroxyguanine glycosylase-1 (HOGG1)gene of repair DNA and the radiosensitivity in esophageal squamous cell carcinoma(ESCC).Methotis Genome DNA was exracted from whole blood cells of ESCC patients.XRCC3 and HOGG1 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method.The relationship was analyzed between SNP of XRCC3 Thr242 Met,HOGG1 Ser326 Cys and the response to radiotherapy in ESCC.Results Totally 199 ESCC patients were treated with radical radiotherapy.The response rate w88 81.4%.The response rate in patients with the XRCC3 Thr/Met genotype was significant higher than that in patients with Thr/Thr genotype(91.5%vs 77.1%,X2=5.67,P=0.017),with the same in HOGGlSet/Ser,Ser/Cys and Cys/Cys genotype(74.1%,84.2%,83.9%,X2=2.64,P=0.268).The esophageal radioactivity injury rate in patients with the XRCC3 Thr/Met genotype was also significant higher than that in patients with Thr/Thr genotype(35.6%vs 20.0%,X2=5.44,P= 0.020),with the same in HOGG1 Ser/Ser,Ser/Cys and Cys/Cys genotype(24.1%,24.6%,25.8%,X2=0.03,P=0.984).In Iogistic multivariate analysis,the SNP of XRCC3 was the independent influencing factor closely correlating with the mdiosensitivity of esophageal cancer(X2=16.12,4.43,P=0.009.0.035).No significant difierence was observed between the SNP in HOGG1 Ser326 Cys and the response rate of radiotherapy or the rate of esophageal radioactivity injury(X2=3.74,0.58,P=0.053,0.445).Conclusions SNP of XRCC3 Thr/Met is associated with the radiosensitivity in ESCC patients,which suggests that the XRCC3 Thr/Met SNP may be a predictor for ESCC patients who likely to response to radiotherapy.

The WD40 domain exhibits a β-propeller architecture, often comprising seven blades. The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes. In this review, we will discuss the identification, definition and architecture of the WD40 domains. WD40 domain proteins are involved in a large variety of cellular processes, in which WD40 domains function as a protein-protein or protein-DNA interaction platform. WD40 domain mediates molecular recognition events mainly through the smaller top surface, but also through the bottom surface and sides. So far, no WD40 domain has been found to display enzymatic activity. We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins. In the last part of this review, we will discuss how post-translational modifications are recognized by WD40 domain proteins.
Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Humans ; Molecular Sequence Data ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Proteins ; chemistry ; metabolism ; Repetitive Sequences, Amino Acid

Objective To synthesize a dual-function nanodrug with immunosuppression of tacrolimus (FK506) and lubrication of artificial tear carboxymethylcellulose sodium (CMC), and provide a basis for the clinical treatment of dry eye syndrome. Methods The FK506 nanocrystals were prepared by ultrasonic method, and polyallylamine hydrochloride (PAH) and CMC were deposited alternatively on the surface of FK506 nanocrystals using layer-by-layer (LbL) self-assembly technology to prepare the bifunctional nanodrug. The morphology, particle size, surface charge, and composition of the nanodrug were analyzed. Results The particle size of FK506 nanocrystals was uniform, and the FK506-(PAH/CMC)3 was approximately spherical with uneven surface. Zeta potential detection results showed that the charge changed alternatively with the increasing of layer number. The results of laser scanning confocal imaging and infrared spectroscopy showed that PAH and CMC were successfully modified on the surface of FK506 nanocrystals. Conclusion The prepared FK506-(PAH/CMC)3 nanodrug is expected to provide a scientific basis for the combined treatment of dry eye.

Objective To evaluate the effect of anti-microbia-l coated central venous catheter (CVC),compared with routine CVC,on catheter-associated deep venous thrombosis (CADVT). Methods A total of 1 359 patients,aged 26-82 years,ASA physical status Ⅰ-Ⅲ,undergoing internal jugular,axillary-subclavian,or femoral vein CVC catheterization during January to June of 2017,were retrospectively reviewed.The patients were divided into intoanti-microbial-coated CVC group (group A)and routine CVC group (group B).Gender,age,ASA class,pre-operative risk of thrombus (Caprini score),CVC site,surgical site,ultrasound-guided catheterization,and anticoagu-lation therapy,CADVT and the degree,as well as the other adverse events were recorded.Results A total of 938 patients were successfully matched.There were 323 (34.4%)articipants diagnosed with CADVT with bedside point-of-care ultrasound,in which 172 cases (36.7%)in group A and 151 (32.2%)in group B.There was no statistical significance of CADVT and the degree between the two groups.The subgroup analysis results indicated that the patients using anti-microbial-coated CVC with high risk of thrombus (Caprini score ≥ 5 points)(OR 1.34,95% C I 1.01-1.78),undergoing catheterization according to anatomical landmark (OR 1.69,95% C I 1.04-2.74),and not-receiving anticoagulation therapy (OR 1.39,95% C I 1.01-1.92)had an increased risk of CADVT compared with those using routine CVC.A significantly decreased incidence of catheter-associated infection in group A was observed compared with group B (0.9% vs 4.1%,P<0.05).Conclusion Anti-micro-bial-coated CVC does not increase the incidence of CADVT.

Objective To study the effect of scalp acupuncture plus facilitation technique on the temporal and spatial parameters of gait in spastic cerebral palsy. Method Thirty eligible patients with spastic cerebral palsy were randomized into a treatment group and a control group based on the inter-group balance in age, palsy type, and the Gross Motor Function Classification System (GMFCS), 15 cases in each group. The treatment group was intervened by scalp acupuncture, together with the facilitation technique during the retaining of the needles; the control group was also by scalp acupuncture and facilitation techniques but with over 1 h interval between the two methods. The treatment was given once a day, totally for 3 months. The walking, running, and jumping items (E category) of the Gross Motor Function Measure-66 (GMFM-66), temporal and spatial parameters of gait, and vertical ground reaction force during stance were compared before and after the treatment. Result There were no significant inter-group differences in comparing the rates of E category of the GMFM-66 before the treatment (P>0.05), the rates were significantly changed after the treatment in both groups (P<0.05), and there were significant differences in comparing the rates between the two groups after the intervention (P<0.05);after the intervention, the step length, walking speed, and step frequency were increased significantly in both groups (P<0.05), while the double-stance phase was decreased significantly, and swing phase was increased significantly (P<0.05); after the intervention, the step length, walking speed, and step frequency of the treatment group were significantly better than that of the control group (P<0.05). Conclusion Acupuncture plus facilitation technique can mitigate the spasticity in spastic cerebral palsy, improve the gross motor function, especially the function of standing and walking, enhance the activities, and benefit the improvement of the step length, step width, and walk speed.

Objective:To evaluate the clinical curative effect of self-made Lishi Qufeng Juanbi Decoction combined with Febuxostat tablet on uric acid nephropathy (UAN).Methods:Randomized controlled trial. A total of 150 patients with UAN in Yixing Hospital of Traditional Chinese Medicine were enrolled as the observation objects between October 2019 to October 2021. According to random number table method, they were divided into two groups, 75 in each group. The control group was treated with Febuxostat tablets on basis of routine diet intervention, while the observation group was treated with self-made Lishi Qufeng Juanbi Decoction on basis of control group. All were continuously treated for 6 months. TCM syndromes were scored before and after treatment. The levels of serum uric acid (SUA) and creatinine (SCr) were detected by full-automatic biochemical analyzer, and levels of serum CRP, IL-6 and IL-8 were detected by ELISA. The 24h urine was collected to detect 24 h urine protein quantitation. The adverse events were recorded, and clinical curative effect was evaluated.Results:There were significant differences in total response rate between observation group and control group [93.33% (70/75) vs. 80.00% (60/75); χ2=5.77, P=0.016]. After treatment, scores of waist soreness-fatigue and frequent nocturia in observation group were significantly lower than those in the control group ( t=9.17, 2.67, P<0.01), and frequency of joint swelling pain was significantly lower than that of the control group ( t=9.49, P<0.01). The levels of serum SUA and SCr, and 24 h urine protein quantitation in observation group were significantly lower than those in the control group ( t=3.38, 2.49, 12.55, P<0.01 or P<0.05), and levels of CRP, IL-6 and IL-8 were significantly lower than those in the control group ( t=5.44, 4.15, 9.61, P<0.01). There was no significant difference in incidence of adverse reactions between observation group and control group [4.00% (3/75) vs. 10.67% (8/75); χ2=2.45, P=0.117]. Conclusion:The self-made Lishi Qufeng Juanbi Decoction combined with Febuxostat tablets can promote uric acid metabolism, improve high uric acid environment, protect renal function, inhibit the release of inflammatory factors, improve curative effect and reduce adverse reactions in UAN patients.

BackgroundPsychological capital has a significant impact on individual post-traumatic growth and well-being. However， there is limited research on the psychological capital and its related factors among parents of children with leukemia. ObjectiveTo explore the psychological capital status of parents of children with leukemia and analyze its influencing factors， in order to provide references for formulating intervention strategies to improve the psychological capital among these parents. MethodsFrom March 2021 to April 2022， 143 parents of children diagnosed with leukemia from the Department of Pediatrics at the First Affiliated Hospital of Xinjiang Medical University was selected. The general demographic information questionnaire， Positive Psychological Capital Questionnaire （PPQ）， Chinese-Posttraumatic Growth Inventory （C-PTGI） and Index of Well-being Scale （IWB） were used to investigate the participants. Multiple linear regression analysis was used to analyze the influencing factors of psychological capital. ResultsThe PPQ total score for parents of children with leukemia was （113.48±15.80）. The PPQ total score showed positive correlations with the scores of C-PTGI and IWB （r=0.727， 0.598， P<0.01）. The course of children's illness （β=0.136， P=0.017）， parental education level （β=0.139， P=0.012） and C-PTGI score （β=0.622， P<0.01） were influencing factors of psychological capital among these parents， collectively explaining 57.6% of the total variability. ConclusionThe level of positive psychological capital among parents of children with leukemia warrants improvement. Factors including course of the children's illness， parental education level and post-traumatic growth significantly impacted their psychological capital.［Funded by Innovation and Entrepreneurship Project for Graduate Students of Xinjiang Medical University （number， CXCY2022047）］

ObjectiveTo explore the potential mechanism of Zuoguiwan in ameliorating polycystic ovary syndrome （PCOS） by network pharmacology and liquid chromatography-mass spectrometry （LC-MS）-based metabolomics. MethodThe active ingredients and potential targets of Zuoguiwan for treating PCOS were predicted by bioinformatics. SD rats were assigned into a control group and a modeling group. The rat model of PCOS was established by gavage with letrozole （1 mg·kg^-1） combined with feeding with a high-fat diet. At the end of modeling， the modeled rats were assigned into model （normal saline）， metformin （300 mg·kg^-1）， and Zuoguiwan （concentrate 1.62 g·kg^-1） groups. The body weight and oestrous cycle of each rat were recorded， and the ovary was stained with hematoxylin and eosin for observation of ovarian morphology. Enzyme-linked immunosorbent assay was employed to determine the serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-mullerian hormone （AMH）， testosterone （T）， and estradiol （E₂）， and the LH/FSH ratio was calculated. Serum metabolomics of rats was conducted by orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen the metabolite-enriched pathways. Furthermore， network pharmacology and association analysis were employed construct the compound-response-enzyme-gene network. ResultA total of 503 potential targets of Zuoguiwan and 5 843 targets of PCOS were screened out， with 271 common targets. The Gene Ontology enrichment analysis revealed that the common targets were involved in the response to lipopolysaccharide， etc.， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment yielded 119 pathways. Animal experiments showed that compared with the control group， the model group presented increased body weight （P<0.01）， elevated LH and AMH levels （P<0.01）， increased LH/FSH ratio （P<0.01）， lowered E₂ level （P<0.01）， and increased cystic follicles. Compared with the model group， Zuoguiwan and metformin decreased the body weight （P<0.01）， reduced atretic follicles and cystic follicles， increased mature follicles and corpus luteum， and thickened the granulosa layer. Moreover， Zuoguiwan lowered the T， FSH， LH， and AMH， and LH/FSH levels （P<0.01） and elevated the E₂ level （P<0.01）. The principal component analysis and OPLS-DA in metabolomics showed that the differential metabolites between Zuoguiwan and model groups included 26 up-regulated metabolites in the Zuoguiwan group. There were 8 common pathways predicted by the KEGG enrichment analysis in network pharmacology and the metabolite enrichment in metabolomics. The results of topological analysis revealed the pathways of steroid hormone biosynthesis and glycerol-phospholipid metabolism， and the constructed compound-response-enzyme-gene network revealed that the key targets were protein kinase B1 （Akt1）， epithelial growth factor receptor （EGFR）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and mitogen-activated protein kinase 1 （MAPK1）. ConclusionZuoguiwan regulated the steroid hormone biosynthesis pathway to recover hormone levels， promote follicle production and development， and improve ovarian function， which may be the potential mechanism of this medicine in treating PCOS.

ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure （POF） based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank， model， and low- and high-dose （2， 8 g·kg^-1， respectively） Zuoguiwan groups， with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg^-1 on the first day and 8 mg·kg^-1 from the second day to the fifteenth day for the modeling of POF. After modeling， the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone （FSH）， estradiol （E₂）， luteinizing hormone （LH）， anti-Mullerian hormone （AMH）， malondialdehyde （MDA）， catalase （CAT）， superoxide dismutase （SOD）， and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， ferritin heavy chain （FTH1）， and acyl-CoA synthetase long chain family member 4 （ACSL4）. ResultCompared with the blank group， the model group showcased significantly increased atretic follicles， atrophied， fragmented， and vacuolated mitochondria， and reduced， loose， and disordered cristae in mitochondria. Compared with the model group， high-dose Zuoguiwan increased mature follicles， the volume of mitochondria in the ovary， alleviated the vacuolation， and improved the number and arrangement of mitochondrial cristae. Compared with the blank group， the modeling elevated the levels of iron， MDA， FSH， and LH， up-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， decreased the activities of SOD and CAT， lowered the levels of E₂ and AMH， and down-regulated the expression of ACSL4 （P<0.05， P<0.01）. Compared with the model group， drug interventions lowered the levels of iron， MDA， FSH， and LH， down-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， increased the activity of CAT， elevated the levels of E₂ and AMH， and up-regulated the expression of ACSL4 （P<0.05， P<0.01）. ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis， thereby improving the ovarian function of POF rats.

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg^-1·d^-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg^-1·d^-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E₂， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.